Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade
文献类型：期刊论文
| 作者 | Hyman, JM; Firestone, AJ; Heine, VM; Zhao, Y; Ocasio, CA; Han, K; Sun, M; Rack, PG; Sinha, S; Wu, JJ |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2009 |
| 卷号 | 106期号:33页码:14132-14137 |
| 关键词 | antagonist cancer Gli medulloblastoma |
| 通讯作者 | Chen, JK (reprint author), Stanford Univ, Sch Med, Dept Chem & Syst Biol, 269 Campus Dr,CCSR 3155, Stanford, CA 94305 USA.,jameschen@stanford.edu |
| 英文摘要 | Inappropriate activation of the Hedgehog (Hh) signaling pathway has been implicated in a diverse spectrum of cancers, and its pharmacological blockade has emerged as an anti-tumor strategy. While nearly all known Hh pathway antagonists target the transmembrane protein Smoothened (Smo), small molecules that suppress downstream effectors could more comprehensively remediate Hh pathway-dependent tumors. We report here four Hh pathway antagonists that are epistatic to the nucleocytoplasmic regulator Suppressor of Fused [Su(fu)], including two that can inhibit Hh target gene expression induced by overexpression of the Gli transcription factors. Each inhibitor has a unique mechanism of action, and their phenotypes reveal that Gli processing, Gli activation, and primary cilia formation are pharmacologically targetable. We further establish the ability of certain compounds to block the proliferation of cerebellar granule neuron precursors expressing an oncogenic form of Smo, and we demonstrate that Hh pathway inhibitors can have tissue-specific activities. These antagonists therefore constitute a valuable set of chemical tools for interrogating downstream Hh signaling mechanisms and for developing chemotherapies against Hh pathway-related cancers. |
| 学科主题 | Science & Technology - Other Topics |
| 类目[WOS] | Multidisciplinary Sciences |
| 关键词[WOS] | BASAL-CELL CARCINOMA ; SONIC-HEDGEHOG ; MEDIATED TRANSCRIPTION ; SIGNALING MOLECULES ; SMOOTHENED ACTIVITY ; PRIMARY CILIUM ; IN-VITRO ; GLI2 ; MEDULLOBLASTOMA ; SUPPRESSOR |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000269078700091 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1289]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Hyman, JM,Firestone, AJ,Heine, VM,et al. Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2009,106(33):14132-14137. |
| APA | Hyman, JM.,Firestone, AJ.,Heine, VM.,Zhao, Y.,Ocasio, CA.,...&Chen, JK.(2009).Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,106(33),14132-14137. |
| MLA | Hyman, JM,et al."Small-molecule inhibitors reveal multiple strategies for Hedgehog pathway blockade".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 106.33(2009):14132-14137. |
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